Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acidic fibroblast growth factor (aFGF) in rat cerebrospinal fluid (CSF) increased 1000 times in the 2 hr period after food intake, or intraperitoneal (IP) or intracerebroventricular (ICV) glucose infusion. It diffused into the brain parenchyma and was taken up into neurons in the hypothalamus, hippocampus, etc.... aFGF is produced in the ependymal cells and released into CSF in response to increased glucose. ICV application of aFGF dose dependently inhibits, and anti-aFGF antibody facilitates food intake. IP injection of glucose 2 hr before a task that combined acquisition with passive avoidance significantly increased retention of avoidance by mice tested 24 hr later. In a Morris water maze task, IP glucose injection 2 hr before a first trial block reduced time to find and climb onto a platform hidden just below the water surface. These facilitation by glucose of affective and spatial memory were abolished by pretreatment with anti-aFGF antibody applied ICV. Continuous ICV infusion of aFGF into rats also significantly increased the reliability of passive avoidance for several days. The memory facilitation by aFGF was significantly attenuated by CA1 neuron death in the hippocampus caused by 5 min ischemia of the brain, in gerbils. After food intake, centrally-released aFGF reaches the hippocampus and facilitates memory, while peripherally released cholecystokinin reaches the endings of the afferent vagal nerves in the portal vein and changes the vagal nerve activity, which modulates hippocampal activity, to lead to memory facilitation. This, however, is blocked by vagotomy below the diaphragm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pathophysiological significance of brain acidic fibroblast growth factor. 128 50

The neuroprotective action of a cholecystokinin octapeptide analogue, ceruletide, was evaluated in models of cerebral ischemia using Mongolian gerbils. Ceruletide significantly suppressed the hyperactivity and amnesia induced by ischemia when injected s.c. 30 min before 5-min occlusion of the bilateral common carotid arteries at room temperature or immediately after their reperfusion. Ceruletide also reduced behavioral changes in ischemic gerbils whose body temperature was maintained at 37 degrees C during the 3-min occlusion. In these groups, delayed neuronal cell death in the hippocampal CA1 area following ischemia was markedly attenuated by s.c. administration of ceruletide. On the other hand, ceruletide could not inhibit the behavioral changes or the neurodegeneration induced in the hippocampal CA1 area by 5-min occlusion at 37 degrees C. These findings indicate that peripheral injection of ceruletide produces a neuroprotective action against moderate cerebral ischemia, which is the first evidence suggesting the efficacy of ceruletide in neurodegenerative diseases.
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PMID:Systemic administration of a cholecystokinin analogue, ceruletide, protects against ischemia-induced neurodegeneration in gerbils. 151 36

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
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PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

In a variety of animal models of acute pancreatitis, cholecystokinin-receptor antagonists have ameliorated the injury response. These results suggest that cholecystokinin may play a primary role in the pathogenesis of pancreatitis initiated by multiple stimuli. In an effort to test this theory, a sensitive and high affinity cholecystokinin-receptor antagonist L364,718 was administered to four different models of acute pancreatitis that were produced in the ex vivo perfused canine pancreas preparation. The four models of pancreatitis were initiated by cerulein infusion, partial duct obstruction with secretin stimulation, oleic acid infusion, and a 2-hour period of ischemia. In each model, pancreatitis was manifest by edema formation, weight gain, and hyperamylasemia during a 4-hour perfusion. In cerulein infusion-induced pancreatitis L364,718 inhibited edema formation and weight gain (31 +/- 5 gm versus 7 +/- 6 gm; p less than 0.05) and significantly decreased plasma amylase activity (36,605 +/- 21,216 U/dl versus 9421 +/- 5149 U/dl; p less than 0.05). The acute pancreatitis induced by the other three stimuli was not ameliorated by L364,718 treatment. We conclude that in the ex vivo-perfused canine pancreas preparation cerulein-induced pancreatitis is mediated at least in part by the cholecystokinin receptor. Early blockade of the cholecystokinin receptor was of no benefit in treating the other models of pancreatitis, suggesting that cholecystokinin is not involved in the early pathogenesis.
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PMID:The role of cholecystokinin in the pathogenesis of acute pancreatitis in the isolated pancreas preparation. 170 26

The effects of transient (30') forebrain ischemia (4 vessel occlusion model) on peptidergic neurons and astroglial cells in various diencephalic and telencephalic areas have been analyzed. The study was performed at various time intervals of reperfusion, i.e. 4 h, 1, 7 and 40 days. Neuropeptide Y (NPY), somatostatin (SRIF), cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP) and arginine-vasopressin (AVP) immunoreactive (IR) neuronal systems and glial fibrillary acidic protein (GFAP)-IR glial cells have been visualized by means of the indirect immunoperoxidase procedure using the avidin-biotin technique. The analysis was performed by means of computer assisted microdensitometry and manual cell counting. At the hippocampal level a huge reduction of neuropeptide (CCK, SRIF, VIP) IR cell bodies was observed, still present 40 days after reperfusion. On the contrary, in the frontoparietal cortex the number of the neuropeptide (CCK, SRIF, VIP, NPY) IR neurons showed a decrease at 4 h, 1 and 7 days after reperfusion followed by a complete recovery at 40 days. A rapid reduction followed by an almost complete recovery (7 days after reperfusion) was also observed at striatal level where SRIF- and NPY-IR neurons were detected. A marked decrease of NPY-IR terminals was observed in the paraventricular and periventricular hypothalamic nuclei and in the paraventricular thalamic nucleus. AVP-IR was markedly reduced in the magnocellular part of the paraventricular nucleus throughout the analyzed period (7 days after reperfusion). GFAP-IR was increased in the hippocampal formation and neostriatum while a not consistent increase was observed at neocortical level. These data point to a differential recovery of peptide-IR and to a different astroglial response in the various brain areas after transient forebrain ischemia. Region-specific factors rather than factors related to neuronal chemical coding seems to play a major role in determining the vulnerability of neuronal populations to transient ischemia.
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PMID:Effects of transient forebrain ischemia on peptidergic neurons and astroglial cells: evidence for recovery of peptide immunoreactivities in neocortex and striatum but not hippocampal formation. 197 43

Previous studies using the isolated ex vivo perfused canine pancreatitis preparation showed that during a 4-hour perfusion pancreatitis (edema, weight gain, hyperamylasemia) can be induced by four different stimuli. The stimuli include the intra-arterial infusion of oleic acid (FFA), a 2-hour period of ischemia before perfusion (ISCH), partial obstruction of the pancreatic duct with secretin stimulation (POSS), and the intra-arterial infusion of cerulein at supramaximal doses (CER). In the present study, changes in high-energy phosphate metabolism, as determined by nuclear magnetic resonance spectroscopy, and changes in cellular structure, determined by light and electron microscopy, were documented for all four models of acute pancreatitis. The control preparations remained stable for the 4-hour perfusion period, with no decrease in adenosine triphosphate (ATP) levels. In the FFA preparations, ATP decreased to 36% of baseline levels during the 4-hour perfusion (p less than 0.001). In the ISCH preparations, ATP decreased to undetectable levels during the 2-hour period of ischemia, but recovered rapidly and remained at baseline levels during the perfusion. ATP levels remained stable in the remaining two models of pancreatitis (POSS, CER). Microscopy demonstrated that the initial injury was located chiefly in the capillaries (swollen endothelium, intravascular thrombi) in the FFA and ISCH preparations. In the POSS and CER preparations, capillary changes were minimal and the injury was located chiefly in the acinar cells (swollen endoplasmic reticulum, zymogen granule depletion, vacuolization). The POSS preparations also showed striking dilation of centroacinar lumens reflecting duct obstruction. In additional studies it was shown that the ATP decline in the FFA preparations could be significantly reduced by pretreatment with free radical scavengers. The morphologic changes could be reduced by free radical scavengers in the FFA and ISCH preparations. Any amelioration of morphologic injury in the POSS preparations was obscured by dilatation of centroacinar lumens in both treated and untreated groups. The morphologic changes in the CER preparations were reduced by treatment with a cholecystokinin inhibitor.
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PMID:Changes in high-energy phosphate metabolism and cell morphology in four models of acute experimental pancreatitis. 200 16

Following vascular occlusion, development of collateral circulation occurs in at least two time-related phases: (1) the fast enhancement of the function of preexisting channels and (2) the slow formation of new vessels. Inasmuch as the renin-angiotensin system can act as a protective mechanism against local ischemia by activating preexisting collateral vessels, it is of interest to establish whether angiotensin II also produces stimulation of new vessel formation. Angiotensin II or cholecystokinin, an unrelated peptide, was incorporated in a slow-release formulation polyacrylamide gel and implanted in a pocket made in the rabbit cornea. Periodic examinations revealed that angiotensin II significantly stimulates new vessel formation; maximum values were attained in approximately 2 to 3 weeks. In contrast, cholecystokinin or polyacrylamide gel alone failed to stimulate any significant new vessel formation. Positive neovascularization was present in 85% of the total number of corneas implanted with angiotensin II, whereas 14% and 8% positive results were seen in the corneas implanted with either cholecystokinin or polyacrylamide gel alone, respectively. It is concluded that angiotensin II not only facilitates the activation of preexisting collateral vascular pathways but also has angiogenic properties and therefore could play an active role not only in the fast but also in the slow phase of the development of collateral circulation.
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PMID:Neovascularization produced by angiotensin II. 257 74

In studies on the pathogenesis of ischemic cell injury and of other pancreatic diseases the knowledge of the actual pancreatic energy state is an important factor. Therefore, it would be advantageous to have a simple and inexpensive method to determine this parameter and its alterations in the pancreas. At uniform hormonal stimulation, the extent of exocrine pancreatic secretion showed a clear dependence on energy supply in this organ. The degree of pancreatic juice edema formed after bolus injection of cholecystokinin and secretin at ductal occlusion was found to be the most sensitive and reproducible measure of the functional capacity of the pancreatic energy metabolism. While this parameter can be applied to experimental studies, only, the juice volume secreted could be determined under clinical conditions, too. Both parameters of pancreatic secretion were clearly decreased after preceding short-term ischemia and recovered after an adequate interval of reperfusion.
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PMID:Pancreatic exocrine secretion--a measure of the functional capacity of the pancreatic energy metabolism. 258 44

Since the mid-1970s, evidence has accumulated that cholecystokinin (CCK) has a role as a neuromodulator or neurotransmitter in the central nervous system as well as in the periphery. CCK has been shown to have a variety of effects on gastrointestinal functions and is one of the main candidates for a role as a peripheral negative feedback signal to stop feeding behavior. CCK produces satiety not only in animals but also in man: it reduces appetite and activation arising from the preparation of a meal and inhibits intake of liquid and solid food in both lean and obese subjects. The closely related peptide caerulein has similar effects. The site of action of peripherally administered CCK seems to be on an abdominal organ innervated by gastric vagal branches and relayed to the brain by afferent vagal fibres, since selective gastric vagotomy blocks the satiety effect, but pharmacological antagonism of vagal motor effects or lesions of the ventromedial hypothalamus do not. CCK also may have a role in the regulation of pain perception. In mice, CCK and caerulein were shown to produce a decrement in response to noxious stimulation after peripheral and central administration. In man, caerulein was demonstrated to relieve pain originating from biliary and renal colic as well as from cancer and ischemia. A series of studies in healthy man revealed that caerulein also alleviates experimentally induced cutaneous pain. Data from animal studies suggest that CCK-like peptides not only are able to produce analgesic effects on their own, but also are involved in the modulation of opioid systems mediating analgesia. Further study of these effects of CCK should elucidate the regulatory connections between the life-sustaining functions of feeding and pain sensation.
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PMID:Effects of cholecystokinin and caerulein on human eating behavior and pain sensation: a review. 308 29

The effects of a thromboxane A2 receptor antagonist, ONO 3708, on ischemia-reperfusion injury of the pancreas were evaluated using an isolated in-vivo-perfused dog pancreas model. Pancreatic endocrine and exocrine function were stimulated with cholecystokinin octapeptide (10(-12) mol). This dose significantly increased endogenous prostaglandin I2 and thromboxane A2 production by the pancreas (both P < 0.001). A period of 60 min of ischemia and subsequent reperfusion induced an increase of pancreatic amylase release (P < 0.01) and a decrease of insulin release (P < 0.01). There was also a decrease of pancreatic juice and pancreatic bicarbonate and amylase output (au P < 0.01), suggesting damage to the acinar, ductular, and beta cells. Intravenous administration of ONO 3708 (200 micrograms/kg/min) throughout the experiment prevented these abnormalities of pancreatic secretion. It also reduced the plasma lipid peroxide level in the venous drainage (P < 0.01) and elevated the prostaglandin I2 level (P < 0.01) without changing thromboxane A2 levels. ONO 3708 thus appeared to protect the pancreas from ischemia-reperfusion injury by reducing the peroxidation of cell membrane lipids and by decreasing the thromboxane A2/prostaglandin I2 ratio, which is a predictor of cellular injury.
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PMID:The effect of a thromboxane A2 receptor antagonist (ONO 3708) on ischemia-reperfusion injury of the dog pancreas. 750 45


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